Neural Circuitry of Motioninduced Nausea

PROJECT SUMMARY Nausea is a queasy sensation that arises from interoception of physiological distress within the body. However, there remains a critical gap in the fundamental understanding of neurons and neural circuits responsible for this debilitating condition. This proposal focuses on motion sickness (originating in the brain) rather than chemically induced nausea (originating in the viscera), thereby providing an innovative, orthogonal view into the cellular and circuit mechanisms of nausea. The overall objective in this application is to understand how motion-induced nausea is elicited in the brain. The central hypothesis posits that specific neurons in the caudal hindbrain are responsible for the sickness. This hypothesis will be tested in mice by addressing the following three specific aims: 1) Establishing the necessity and sufficiency of discrete subsets of hindbrain neurons for motion-induced nausea; 2) Identifying the genetic profile defining hindbrain neurons associated with nausea; and 3) Mapping the presynaptic to and postsynaptic connections from these neurons. The proposed research is significant because it will reveal the molecules, cells, and circuits responsible for motion-induced nausea. The anticipated outcomes of these studies promise unique and powerful inroads into how the mammalian brain processes distress signals from the body and orchestrates responsive measures.